Duration of Benefit for OnabotulinumtoxinA in Treatment of Chronic Migraine

This study has been completed.
Sponsor:
Collaborator:
Allergan
Information provided by (Responsible Party):
Cady, Roger, M.D.
ClinicalTrials.gov Identifier:
NCT02037425
First received: January 14, 2014
Last updated: July 11, 2016
Last verified: July 2016
  Purpose
To obtain a patient specific understanding of response to treatment with onabotulinumtoxinA by collecting and correlating pre and post treatment subject specific history, clinical outcomes, and histological changes.

Condition Intervention Phase
Chronic Migraine
Drug: onabotulinumtoxinA
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Exploratory Study of the Natural History, Clinical Outcomes, and Neuronal Endplate Changes in Subjects Reporting Short Duration vs. Long Duration of Benefit for OnabotulinumtoxinA in Treatment of Chronic Migraine

Resource links provided by NLM:


Further study details as provided by Cady, Roger, M.D.:

Primary Outcome Measures:
  • Subject Global Impression of Change [ Time Frame: Weeks 12, 24, and 36 Post Randomization ] [ Designated as safety issue: No ]
    Changes in the Subject's Global Impression of Change (SGIC) measured at weeks 12, 24, and 36 for Groups A, B, and C. Subject global impression of change was measured on a 7 point scale with 0 being Very Much Worse and 7 Very Much Improved.

  • Duration of onabotulinumtoxinA Over 3 Injection Cycles in Groups A, B, and C [ Time Frame: From day 29 (first day of injection cycle 1) to day 281 (84th day of injection cycle 3) plus or minus 12 days ] [ Designated as safety issue: No ]
    Compare the duration of onabotulinumtoxinA response through the 3 injection cycles of the study for Groups A, B, and C as measured by headache days during each period (Baseline (28 days), Treatment Period 1(84 days), Treatment Period 2(84 days), and Treatment Period 3(84 days). Duration of response is defined as a 30% reduction in the number of headache days compared to baseline.


Secondary Outcome Measures:
  • Headache Days [ Time Frame: From day 29 (first day of injection cycle 1) to day 281 (84th day of injection cycle 3) plus or minus 12 days ] [ Designated as safety issue: No ]
    Comparison of headache days per month over each injection cycle between Groups A, B, and C (Baseline (28 days), Treatment Period 1(84 days), Treatment Period 2(84 days), and Treatment Period 3(84 days). Subjects will remain in their assigned groups based on assessment at 12 weeks.

  • Migraine Disability Assessment Scale (MIDAS) [ Time Frame: Baseline, Week 12, Week 24, and Week 36 Post Randomization ] [ Designated as safety issue: No ]

    Comparison between Group A, B, and C for MIDAS total scores (effect migraine headaches have on subjects daily function) measured at baseline and weeks 12, 24, and 36.

    Total score of disability ranges:

    • 0 to 5, MIDAS Grade I, Little or no disability
    • 6 to 10, MIDAS Grade II, Mild disability
    • 11 to 20, MIDAS Grade III, Moderate disability
    • 21+, MIDAS Grade IV, Severe disability Score ranges from 0-450. No subscales are present.

  • Social Readjustment Rating Scale (SRRS) [ Time Frame: Baseline, Week 12, Week 24, and Week 36 Post Randomization ] [ Designated as safety issue: No ]
    Comparison between Group A, B, and C for SRRS scores (impact of common stressors) measured at baseline and weeks 12, 24, and 36. Scores can range from 0 to an undetermined amount, as subjects are allowed to rate unlisted events according to their own sense of stress. A total lower than 150 suggests a low level of stress and a low probability of developing a stress-related disorder. Scores greater than 150 suggest higher levels of stress and higher probabilities of developing stress-related disorders.

  • Physician Global Impression of Change (PGIC) [ Time Frame: Week 12, Week 24, and Week 36 Post Randomization ] [ Designated as safety issue: No ]
    Comparison between Group A, B, and C for PGIC scores measured at weeks 12, 24, and 36. the PGIC scale scores range from 0-7 with 0 being Very Much Worse and 7 being Very Much Improved. A higher score indicates a greater impression of change.

  • Beck Depression Inventory II (BDI-II) [ Time Frame: Baseline, Week 12, Week 24, and Week 36 Post Randomization ] [ Designated as safety issue: No ]
    Comparison between Group A, B, and C for BDI-II scores measured at baseline and weeks 12, 24, and 36. A total score of 0-10 = these ups and downs are considered normal, 11-16 = mild mood disturbance,17-20 = borderline clinical depression, 21-30 = moderate depression, 31-40 = severe depression, over 40 = extreme depression

  • State-Trait Anxiety Inventory (STAI) [ Time Frame: Baseline, Week 12, Week 24, and Week 36 Post Randomization ] [ Designated as safety issue: No ]
    Comparison between Group A, B, and C for STAI scores measured at baseline and weeks 12, 24, and 36. Scores range from 20-80, with 20 indicating lower levels of anxiety most generally, and 80 indicating higher levels of anxiety most generally.

  • Sleep Quality Question [ Time Frame: Baseline, Week 12, Week 24, and Week 36 Post Randomization ] [ Designated as safety issue: No ]
    Comparison between Group A, B, and C for sleep quality scores measured at baseline and weeks 12, 24, and 36 post-randomization. A single sleep quality question was asked indicating quality of sleep over the past four weeks. The scale ranged from 1-5, with 1 being very poor quality and 5 being very good quality of sleep.

  • Acute Medication Usage [ Time Frame: From day 1 (first day of baseline) to day 281 (84th day of injection cycle 3) plus or minus 12 days ] [ Designated as safety issue: No ]
    Comparison of acute medication usage between Groups A, B, and C during baseline, Treatment Period 1, 2, and 3.

  • Consistency of Response to onbotulinumtoxinA Over Three Injection Cycles [ Time Frame: Weeks 12, 24, and 36 Post Randomization ] [ Designated as safety issue: No ]
    Compare the consistency of duration of onabotulinumtoxinA response by the group assignment at 12 weeks to assessments at 24, and 36 weeks evaluations as measured by the number of responders. A responder is defined as a 30% reduction from baseline in the number of headache days.

  • Duration of onabotulinumtoxinA Over 3 Injection Cycles [ Time Frame: Weeks 9, 10, 11, 12, 21, 22, 23, 24, 33, 34, 35, 36 Post Randomization ] [ Designated as safety issue: No ]
    Compare duration of benefit of onabotulinumtoxinA response through 3 injection cycles as measured by headache days per week (including the last 4 weeks of every injection cycle). A percent of responders was calculated using a 30% reduction of the number of headache days compared to average number of headache per week during baseline.


Other Outcome Measures:
  • Neuronal Regrowth [ Time Frame: Baseline & Week 12 Post Randomization ] [ Designated as safety issue: No ]
    Compare neuronal regrowth in the skin biopsies with duration of benefit of onabotulinumtoxinA in Groups A, B, C from baseline to 12 weeks post randomization. Neuronal regrowth change was scored on a 0-3 point scale with 0 being no change from baseline in regrowth and 3 being significant change from baseline.


Enrollment: 44
Study Start Date: April 2014
Study Completion Date: September 2015
Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
onabotulinumtoxinA
At visit 2, subjects will receive their first treatment at Day 29 (+/-3 days). All subjects will receive 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas. Injections will be repeated at day 113 (+/- 3 days) and at day 197 (+/- 3 days).
Drug: onabotulinumtoxinA
BOTOX® (Formulation Number 9060X) contains 200 International Units (IU) of Clostridium botulinum Toxin Type A, reconstituted with 4 cc of normal saline providing 5 units per 0.1 cc. At visit 2, subjects will receive their first treatment at Day 29 (+/-3 days). All subjects will receive 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas. Injections will be repeated at day 113 (+/- 3 days) and at day 197 (+/- 3 days).
Other Name: Botox

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • male or female 18 years or older.
  • able to read, understand, and sign the informed consent.
  • a negative urine pregnancy test at visit 1, if female, and of childbearing potential. Note: If female of childbearing potential, subject must agree to maintain true abstinence or use one of the listed methods of birth control for the duration of the study: hormonal contraceptive, intrauterine device (IUD), condoms, diaphragm, and/or have a male partner who has undergone a successful vasectomy. The use of barrier contraceptive (condom or diaphragm) should always be supplemented with the use of a spermicide.

Note: To be considered not of childbearing potential, subject must be 6 weeks post-surgical bilateral oophorectomy, hysterectomy, bilateral tubal ligation, postmenopausal for at least one year.

  • at least a one year history of migraine
  • history of chronic migraine (with or without aura) according to the criteria of the International Classification of Headache Disorders (ICHD)-3 for at least 3 months prior to enrollment (Appendix I)
  • able to differentiate migraine headache from any other headache they may experience (e.g., cluster headache)
  • onset of migraine before age 50
  • willing to provide responses to questionnaires and complete the online diary.
  • if taking migraine preventive(s), be on a stable dose of the preventive medication for at least 30 days prior to screening
  • concomitant medication dosages approved by the investigator
  • email and internet access for completion of online diary

Exclusion Criteria:

  • previously used onabotulinumtoxinA as a migraine preventative or has used onabotulinumtoxinA for any other reason during the prior year
  • female who is pregnant, planning to become pregnant during the study period, breast feeding, or is of childbearing potential and not practicing a reliable form of birth control
  • headache disorders outside ICHD-3 defined chronic migraine that cannot be easily distinguished from CM (Appendix I)
  • evidence of underlying pathology contributing to their headaches
  • any medical condition that may increase their risk with exposure to BTX including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other significant disease that might interfere with neuromuscular function
  • profound atrophy or weakness of muscles in the target areas of injection
  • skin conditions or infections at any of the injection sites
  • allergy or sensitivities to any component of the test medication
  • in the opinion of the investigator, has an active major psychiatric disorder including substance abuse and/or substance dependence within the last 12 months as determined by the investigator.
  • Medication Overuse Headache as defined by ICHD-3 criteria for opioid or butalbital containing products (Appendix II)
  • planning or requiring surgery during the study
  • a history of poor compliance with medical treatment
  • currently participating in an investigational drug study or has participated in an investigational drug study within the previous 30 days of the screening visit
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02037425

Locations
United States, Missouri
Clinvest/A Division of Banyan Group, Inc.
Springfield, Missouri, United States, 65807
Sponsors and Collaborators
Cady, Roger, M.D.
Allergan
Investigators
Principal Investigator: Roger K Cady, M.D. Clinvest
  More Information

Responsible Party: Cady, Roger, M.D.
ClinicalTrials.gov Identifier: NCT02037425     History of Changes
Other Study ID Numbers: 13-002AL 
Study First Received: January 14, 2014
Results First Received: December 11, 2015
Last Updated: July 11, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Cady, Roger, M.D.:
Chronic Migraine
onabotulinumtoxinA
Headache
Migraine
Neuronal regrowth
Botox

Additional relevant MeSH terms:
Migraine Disorders
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Botulinum Toxins
Botulinum Toxins, Type A
AbobotulinumtoxinA
OnabotulinumtoxinA
IncobotulinumtoxinA
Acetylcholine Release Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on August 24, 2016